1. Field of the Invention
The invention relates generally to the monitoring of analytes in the body and the transdermal delivery of drugs to the body. More particularly, the invention relates to enhancing the rate of flux of a substance collected from or delivered to a biological tissue through the poration of the skin or other biological membrane and the application of a flux enhancer to the porated biological membrane.
2. Description of Related Art
The transfer of materials across biological membranes is necessary in the practice of a variety of medical and other procedures. For example, to minimize complications resulting from diabetes, diabetics must periodically monitor and control their blood glucose levels. Typically, blood glucose monitoring is achieved by taking a sample of blood or other body fluid, and measuring the glucose level present in the sample. Historically, the samples have been obtained by piercing the skin with a needle or lancet. It is also frequently necessary to deliver a drug through the skin or other biological membrane. Most frequently, drugs are delivered transdermally by injection with a needled syringe. Such invasive sampling and drug delivery methods entail a number of disadvantages, most notably, discomfort and potential infection.
In an effort to address the inherent disadvantages of invasive sampling and delivery methods, several minimally invasive and non-invasive sampling and delivery techniques have been developed. "Minimally invasive," as used herein, refers to techniques in which a biological membrane or tissue is invaded by forming small holes or micropores in the surface of a tissue or membrane, but do not substantially damage the underlying, non-surface portions of the tissue or membrane. As used herein, "non-invasive" refers to techniques not requiring the entry of a needle, catheter, or other invasive medical instrument into the body. It has previously been discovered that blood glucose levels can be determined from an analysis of interstitial fluid, the clear fluid occupying the spaces between cells in the body, samples of which can be obtained through the skin by previously known minimally invasive or non-invasive sampling techniques. Previously known minimally invasive or noninvasive methods of sampling interstitial fluid, however, have not been fully successful for blood glucose monitoring purposes. One challenge facing minimally invasive or non-invasive methods is the ability to acquire a large enough sample of interstitial fluid in a short time to enable accurate glucose measurement with low cost disposable assay techniques.
The skin presents the largest, most readily accessible biological membrane through which an analyte may be collected or a drug delivered. Mucosal and buccal membranes present feasible, but less accessible, sites for collection and delivery. Unfortunately, the skin and, to a somewhat lesser extent, the mucosal and buccal membranes, are highly resistant to the transfer of materials therethrough. The skin generally comprises two main parts: the epidermis and the dermis. The epidermis forms the outer portion of the skin, and itself comprises several distinct layers. The outermost layer of the epidermis, the stratum corneum, is composed of denucleated, keratinized, clear, dead cells, and is typically between 10-30 .mu.m thick. The stratum corneum is chiefly responsible for the skin's barrier properties and, therefore, is the layer of skin forming the primary obstacle to the transdermal flux of analytes out of the body and of drugs or other foreign materials or organisms into the body.
There have been significant advancements made in the transdermal transport of substances across a biological membrane by creating micropores in the biological membrane. See, for example, co-pending U.S. application Ser. No. 08/776,863 filed Feb. 7, 1997, entitled "Microporation of Human Skin for Drug Delivery and Monitoring Applications", the entirety of which is incorporated herein by reference. Nevertheless, there is a need to improve upon these techniques and particularly increase the rate at which substances are transported through a biological membrane.